Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4. Serine/Threonine Kinases (STKs), Cyclin-dependent protein kinase 4 (CDK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of transforming growth factor (TGF)-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma.